פרק 36 Chapter 36 Inherited Metabolic Diseases of the Nervous System

Question 1

Table 36-1
METABOLIC DISORDERS DETECTED BY NEONATAL
SCREENING IN NEW ENGLAND

Answer 1

Question 2

Table 36-2_URINARY SCREENING TESTS FOR METABOLIC DEFECTS USE

Answer 2

Question 3

Table 36-3_LYSOSOMAL STORAGE DISEASES (5)

Sphingolypidosis (12)

Neuronal carotid lipofuscinoses (4)

Glycoproteinases (5)

Mucolipidosis (4)

Other lysosomal diseases (5)

Answer 3

Question 4

Table 36-4
DISEASES DISPLAYING A CHERRY-RED MACULAR SPOT (7)

Answer 4

Question 5

schematic for diagnosis of the inherited metabolic diseases of infancy

Answer 5

Question 6

Table 36-5
DIFFERENTIAL DIAGNOSIS OF POLIODYSTROPHIES OF INFANCY

Answer 6

Question 7

Table 36-6
DIFFERENTIAL DIAGNOSIS OF LEUKODYSTROPHIES OF INFANCY

Answer 7

Question 8

Table 36-7
CLASSIFICATION OF THE MUCOPOLYSACCHARIDOSES

Answer 8

Question 9

Differential diagnosis
of mucopolysaccharidoses
from oligosaccharidoses.

Answer 9

Question 10

Table 36-8
MAJOR SYNDROMES OF ADULT-ONSET INHERITED
METABOLIC DISEASES

Answer 10

Question 11

Table 36-9
THE MAJOR CATEGORIES OF MITOCHONDRIAL DISORDERS

Answer 11

Question 12

באיזו מחלה חסר אנזים גלקטוצרברוזידאז?
1. MLD
2. KRABBE
3. SSPE
4. GBS

Answer 12

KRABBE

החסר באנזים גורם להצטברות גלקטוצרברוזיד

מקרא לציורים:
* ירוק –כוראה
* צהוב –אטקסיה
* כחול :סימנים פירמידליים
* שוט – שמחזיקים-AD שנחבטים –AR
* משקפיים –עיוורון
* אוזניות-פגיעה בשמיעה
* גפיים בכתום-פולינירופתיה
* כובע-ורוד-שינוי התנהגותי
* צירים –EPS
* ברקים כחולים –מיוקולוניות
* שן אחת –דמנציה
* שפם –גנטיקה XLINKED
* אדום –מיופתיה?

• דגנר\קטיבי – כחול טאופאטיה ,צהוב סינקלופתיה
• פסים ורודים –דרמטולוגיה
• אדום ורוד -פוליניורופתיה

Question 13

MLDמהיהיהגילהתייצגותמאוחריותר?
1. מוטציהבשניO
2. מוטציהבשניR
3. מוטציהאחתבOואחתבR
4. מוטציהOואללנוסףתקין

Answer 13

4. מוטציה אחת על O ואלל אחד תקין
   כי מדובר במחלה אוטוזומלית רצסיבית

מקרא לציורים:
* ירוק –כוראה
* צהוב –אטקסיה
* כחול :סימנים פירמידליים
* שוט – שמחזיקים-AD שנחבטים –AR
* משקפיים- עיוורון
* אוזניות-פגיעה בשמיעה
* גפיים בכתום-פולינירופתיה
* כובע-ורוד-שינוי התנהגותי
* צירים –EPS
* ברקים כחולים –מיוקולוניות
* שן אחת- דמנציה
* שפם –גנטיקה XLINKED
* אדום –מיופתיה?

• דגנר\קטיבי – כחול טאופאטיה ,צהוב סינקלופתיה
• פסים ורודים –דרמטולוגיה
• אדום ורוד -פוליניורופתיה

Ariel likes detroying colours by cutting them ,he dosent like to talk about it ,it makes him unsteady and feel stupid so he trembles with rage , he cant see whats wrong with I

Ariel=arylsulfatase Destroying colours - metachromatic leukodystrophy Cutting - diagnosis by biopsy Dosent like to talk - decreased fluency , dysarthria Unstaedy- ataxia Stupid- cogitive regression Trembles - intention tremor Cant see - optic atrophy

Question 14

מטופל התקבל בתמונה של כוראה- אתטוזיס, בבדיקתו ספסטיות ב 4 גפיים, ירידה קוגניטיבית , נמצאו נגעים טופים על גבי האוזניים, יש פגיעה עצמית בשפתיים. איזה אנזים קשור במחלה?
א. xanthine oxidase
ב. hypoxanthine guanine phosphorobosyl transferase
ג. alpha neuroaminidase
ד. ATPase

Answer 14

Lesch Nyhan syndrome- Hypoxanthine guanine phophoribosyl transferase (HPRT)

מקרא לציורים:
* ירוק –כוראה
* צהוב –אטקסיה
* כחול :סימנים פירמידליים
* שוט – שמחזיקים-AD שנחבטים –AR
* משקפיים –עיוורון
* אוזניות-פגיעה בשמיעה
* גפיים בכתום-פולינירופתיה
* כובע-ורוד-שינוי התנהגותי
* צירים –EPS
* ברקים כחולים –מיוקולוניות
* שן אחת –דמנציה
* שפם –גנטיקה XLINKED
* אדום –מיופתיה?

• דגנר\קטיבי – כחול טאופאטיה ,צהוב סינקלופתיה
• פסים ורודים –דרמטולוגיה
• אדום ורוד -פוליניורופתיה

Professor les impulsive and aggressive behavior hurts himself ,he tries to keep his moth shut by biting on his lips but al that makes him do is spasm and tremble out of control ,he gets it from his mother who didn’t listen because her hrpt want

: Les- lesch nyhan Impulsive and agressiveMouth shut - self injuries to lips Spasm tremble- spastic choreoathesis Mother- xlr Hrpt - hyposanthine guanine phosph……

Question 15

מטופל עם דמנציה ושינויים באישיות, מפתח מיוקלוניות, סימנים פירמידלים וכן אקסטראפירמידלים. לקרוב משפחה שלו היו שינויים ברשתית של העין.
במה מדובר?

Answer 15

מחלת KUFS

מקרא לציורים:
* ירוק –כוראה
* צהוב –אטקסיה
* כחול :סימנים פירמידליים
* שוט – שמחזיקים-AD שנחבטים –AR
* משקפיים –עיוורון
* אוזניות-פגיעה בשמיעה
* גפיים בכתום-פולינירופתיה
* כובע-ורוד-שינוי התנהגותי
* צירים –EPS
* ברקים כחולים –מיוקולוניות
* שן אחת –דמנציה
* שפם –גנטיקה XLINKED
* אדום –מיופתיה?

• דגנר\קטיבי – כחול טאופאטיה ,צהוב סינקלופתיה
• פסים ורודים –דרמטולוגיה
• אדום ורוד -פוליניורופתיה

Question 16

חולה מתבגר (חשוב לפי הספר - ביטוי שונה לפי גיל) - הפרעה קוגניטיבית, הגדלת אברים, אטקסיה, חולשת גפיים עם אטרופיה ופסיקולציות, בבדיקת עיניים יש cherry red spot.
1. מחלת GM2 הקסואמינידאז
2. סיליאזידוסים
3. מחלת GM1 גנגליזידוסיז.

Answer 16

GM2 הקסואמינידז

Question 17

תיאור של מטופל בוגר עם אטאקסיה ועוד ועוד והפרעה בתנועות עיניים הוריזונטליות
1. גושה
2. נימן פיק
3. טיזקס

Answer 17

גושה
(שיתוק מבט הוריזונטלי)

Question 18

כל הממצאים הנוירולוגים הבאים שכיחים ב
late onset Gaucher Disease
פרט ל:
1. פרכוסים
2. הפרעה סופרנוקלארית בתנועות עיניים
3. הגדלה של הטחול
4. אטקסיה צרבלרית
5. דמנציה

Answer 18

דמנציה אינה אופיינית למחלת גושה

so-called Gaucher disease type III, may begin in childhood, between 3 and 8 years of age. The clinical picture is variable and *combines features of infantile Gaucher disease—such as abducens palsies, dysphagia, trismus, rigidity of the limbs, and dementia—with features of the late childhood–early adult form, such as palsies of horizontal gaze, diffuse myoclonus, generalized seizures, and a chronic course. The diagnosis is established by the finding of splenomegaly, Gaucher cells, glucocerebroside storage, and deficient activity of glucocerebrosidase in leukocytes or cultured fibroblasts.

type of Gaucher disease is occasionally encountered in which seizures, severe diffuse myoclonus, supranuclear gaze disorders (slow saccades, saccadic and pursuit horizontal gaze palsies), and cerebellar ataxia begin in late childhood, adolescence, or adult life. The course is slowly progressive. The intellect is relatively spared. The spleen is enlarged. The pathologic and biochemical abnormalities are the same as those of Gaucher disease of earlier onset

מקרא לציורים:
* ירוק –כוראה
* צהוב –אטקסיה
* כחול :סימנים פירמידליים
* שוט – שמחזיקים-AD שנחבטים –AR
* משקפיים –עיוורון
* אוזניות-פגיעה בשמיעה
* גפיים בכתום-פולינירופתיה
* כובע-ורוד-שינוי התנהגות
* צירים –EPS
* ברקים כחולים –מיוקולוניות
* שן אחת –דמנציה
* שפם –גנטיקה XLINKED
* אדום –מיופתיה?

• דגנר\קטיבי – כחול טאופאטיה ,צהוב סינקלופתיה
• פסים ורודים –דרמטולוגיה
• אדום ורוד -פוליניורופתיה

Question 19

בן 12 סובל מקושי בהליכה מזה מספר חודשים. מגיל 9 סובל מאירועים חוזרים של הקאות, מזה שנתיים קיימת הדרדרות משמעותית בלימודים עם שינויי התנהגות, כגון בכי וצחוק לא תואמים. לאחרונה אירועים של עלפון עם ירידה משמעותית של לחץ דם. נוירולוגית: Intentional tremor, והליכה אטקטית. כללית: היפרפיגמנטציה ברירית הפה, בעור וסביב הפטמות, המרפקיים והברכיים. לנבדק אחות מבוגרת יותר סובלת מחולשת ספסטית ברגליים בלבד.

1. Metachromatic leucodystrophy
2. Adrenoleucodystrophy
3. Sudanopilic leucodystrophy
4. Globoid cell leucodystrophy
5. Trichopolic leucodystrophy

Answer 19

Adrenoleukodystrophy

This disorder traditionally combines a cerebral leukodystrophy and Addison disease, transmitted as an X-linked recessive trait
The fundamental defect is impairment in peroxisomal oxidation of very-long-chain fatty acids (VLCFAs), leading to their accumulation in the brain and adrenal glands. The deficient membrane protein, encoded by a gene that maps to chromosome X28, is a peroxisomal membrane transporter (ABCD1). The gene is located close to the gene for color vision. In the typical X-linked adrenoleukodystrophy (ALD), there is an inability to metabolize VLCFAs,

The *onset is usually between 4 and 8 years, sometimes later; in the most common form of this disorder, only males are affected with the entire syndrome (women carriers may display a special myelopathy discussed further on). The signs of either the adrenal insufficiency or the cerebral lesion may be the first to appear. bronzing of the skin of the hands appeared at 4 years of age; quadriparesis, with dysarthria and dysphagia (i.e., pseudobulbar palsy), became evident at 7 years; a single seizure occurred at 8 years; and by 9 years, shortly before death, the patient was decerebrate and unresponsive. episodic vomiting, decline in scholastic performance and change in personality with inappropriate giggling and crying. After a time, severe vomiting and an episode of circulatory collapse occurred, following which the gait became unsteady and arms ataxic with an intention tremor. Only then did the addisonian increase of pigmentation of the oral mucosa and the skin around nipples and over elbows, knees, and scrotum become evident. Cortical blindness follows in some instances. The late stages are marked by bilateral hemiplegia (at first asymmetrical), pseudobulbar paralysis, blindness, deafness, and impairment of all higher cerebral functions.

מקרא לציורים:
* ירוק –כוראה
* צהוב –אטקסיה
* כחול :סימנים פירמידליים
* שוט – שמחזיקים-AD שנחבטים –AR
* משקפיים –עיוורון
* אוזניות-פגיעה בשמיעה
* גפיים בכתום-פולינירופתיה
* כובע-ורוד-שינוי התנהגות
* צירים –EPS
* ברקים כחולים –מיוקולוניות
* שן אחת –דמנציה
* שפם –גנטיקה XLINKED
* אדום –מיופתיה?

• דגנר\קטיבי – כחול טאופאטיה ,צהוב סינקלופתיה
• פסים ורודים –דרמטולוגיה
• אדום ורוד -פוליניורופתיה

Question 20

תיאור של בחור צעיר עם ספסטיות קשה, פיגור, עירון קורטיקלי, נתרן נמוך ואשלגן גבוהים בדם.
1. טיפול אנזימטי חליפי
2. השתלת מח עצם
3. דיאטה דלת חלבון

Answer 20

השתלת מח עצם- הטיפול היחיד שהוכח כי עוצר ואף משפר חלקית את המחלה
Adrenoleukodystrophy

This disorder traditionally combines a cerebral leukodystrophy and Addison disease, transmitted as an X-linked recessive trait
The fundamental defect is impairment in peroxisomal oxidation of very-long-chain fatty acids (VLCFAs), leading to their accumulation in the brain and adrenal glands. The deficient membrane protein, encoded by a gene that maps to chromosome X28, is a peroxisomal membrane transporter (ABCD1). The gene is located close to the gene for color vision. In the typical X-linked adrenoleukodystrophy (ALD), there is an inability to metabolize VLCFAs,

The *onset is usually between 4 and 8 years, sometimes later; in the most common form of this disorder, only males are affected with the entire syndrome (women carriers may display a special myelopathy discussed further on). The signs of either the adrenal insufficiency or the cerebral lesion may be the first to appear. bronzing of the skin of the hands appeared at 4 years of age; quadriparesis, with dysarthria and dysphagia (i.e., pseudobulbar palsy), became evident at 7 years; a single seizure occurred at 8 years; and by 9 years, shortly before death, the patient was decerebrate and unresponsive. episodic vomiting, decline in scholastic performance and change in personality with inappropriate giggling and crying. After a time, severe vomiting and an episode of circulatory collapse occurred, following which the gait became unsteady and arms ataxic with an intention tremor. Only then did the addisonian increase of pigmentation of the oral mucosa and the skin around nipples and over elbows, knees, and scrotum become evident. Cortical blindness follows in some instances. The late stages are marked by bilateral hemiplegia (at first asymmetrical), pseudobulbar paralysis, blindness, deafness, and impairment of all higher cerebral functions.

מקרא לציורים:
* ירוק –כוראה
* צהוב –אטקסיה
* כחול :סימנים פירמידליים
* שוט – שמחזיקים-AD שנחבטים –AR
* משקפיים –עיוורון
* אוזניות-פגיעה בשמיעה
* גפיים בכתום-פולינירופתיה
* כובע-ורוד-שינוי התנהגות
* צירים –EPS
* ברקים כחולים –מיוקולוניות
* שן אחת –דמנציה
* שפם –גנטיקה XLINKED
* אדום –מיופתיה?

• דגנר\קטיבי – כחול טאופאטיה ,צהוב סינקלופתיה
• פסים ורודים –דרמטולוגיה
• אדום ורוד -פוליניורופתיה

Question 21

בת 38 , מזה מספר שנים סובלת מקשי הליכה ושליטה על השתן. בבדיקה קיימת פראפרזיס פירמידלית,
הליכה ספסטית. שיער הראש דליל.
אחיה נפטר בגיל ההתבגרות כאשר הוא היה מרותק למיטה, דמנטי, חירש ועיוור. מה צפוי למצוא
בבדיקת דם של המטופלת?
א. Low level of low density lipoprotein
ב. Lactic acidosis
ג. High level of cholestanol
ד. very long chain fatty acids High levels of

Answer 21

high levels of very long chain fatty acids

Adrenoleukodystrophy

This disorder traditionally combines a cerebral leukodystrophy and Addison disease, transmitted as an X-linked recessive trait
The fundamental defect is impairment in peroxisomal oxidation of very-long-chain fatty acids (VLCFAs), leading to their accumulation in the brain and adrenal glands. The deficient membrane protein, encoded by a gene that maps to chromosome X28, is a peroxisomal membrane transporter (ABCD1). The gene is located close to the gene for color vision. In the typical X-linked adrenoleukodystrophy (ALD), there is an inability to metabolize VLCFAs,

The *onset is usually between 4 and 8 years, sometimes later; in the most common form of this disorder, only males are affected with the entire syndrome (women carriers may display a special myelopathy discussed further on). The signs of either the adrenal insufficiency or the cerebral lesion may be the first to appear. bronzing of the skin of the hands appeared at 4 years of age; quadriparesis, with dysarthria and dysphagia (i.e., pseudobulbar palsy), became evident at 7 years; a single seizure occurred at 8 years; and by 9 years, shortly before death, the patient was decerebrate and unresponsive. episodic vomiting, decline in scholastic performance and change in personality with inappropriate giggling and crying. After a time, severe vomiting and an episode of circulatory collapse occurred, following which the gait became unsteady and arms ataxic with an intention tremor. Only then did the addisonian increase of pigmentation of the oral mucosa and the skin around nipples and over elbows, knees, and scrotum become evident. Cortical blindness follows in some instances. The late stages are marked by bilateral hemiplegia (at first asymmetrical), pseudobulbar paralysis, blindness, deafness, and impairment of all higher cerebral functions.

מקרא לציורים:
* ירוק –כוראה
* צהוב –אטקסיה
* כחול :סימנים פירמידליים
* שוט – שמחזיקים-AD שנחבטים –AR
* משקפיים –עיוורון
* אוזניות-פגיעה בשמיעה
* גפיים בכתום-פולינירופתיה
* כובע-ורוד-שינוי התנהגות
* צירים –EPS
* ברקים כחולים –מיוקולוניות
* שן אחת –דמנציה
* שפם –גנטיקה XLINKED
* אדום –מיופתיה?

• דגנר\קטיבי – כחול טאופאטיה ,צהוב סינקלופתיה
• פסים ורודים –דרמטולוגיה
• אדום ורוד -פוליניורופתיה

Question 22

אישה בת 40 פנתה לברור בשל חוסר יכולת לעשות פעילות גופנית שגבר לאחרונה.
בבדיקה- נמוכת קומה ותת משקל, שמיעה ירודה, חולשת שרירים קלה, ארפלקסיה. בביופסיית שריר נמצא הממצא הבא. מה האבחנה הסבירה?
1. vasculitis
2. synthetase syndrome/ overlap myositis
3. MELAS
4. CIDP
5. anorexia nervosa

Answer 22

MELAS
* Mitochondrial Encephalomyopathy; Lactic Acidosis; Stroke like episodes.
* mtDNA point mutatuins
* mitochondrial proliferation
* multi system disease.
* axonal neuropathy (areflexia)
* biopsy= ragged red fibers
—–

MELASMitochondrial Encephalomyopathy, lactic acidosis and stroke like episodes

normal early development followed by poor growth, focal or generalized seizures, and recurrent acute episodes that resemble strokes or prolonged transient ischemic attacks.
The stroke deficits often improve but in some cases lead to a progressive encephalopathy.
Some have hemicranial headaches that cannot be distinguished from migraine, and others suffer repetitive vomiting or episodic lactic acidosis.
If there is a characteristic feature it is the unusual clinical pattern of focal seizures, sometimes prolonged, which herald a stroke and produce an unusual radiographic pattern of infarction involving the cortex and immediate subcortical white matter. The CT may also show numerous low-density regions that have no clinical correlates.
Most patients have ragged red fibers in muscle but only rarely is there weakness or exercise intolerance.
Approximately 80 percent of MELAS cases are related to a mitochondrial mutation occurring at the 3243 site of the mitochondrial gene or, in a few instances, at an alternative locus that also codes for a segment of transfer RNA.
Maternal inheritance is common but sporadic cases are well known.
only half of the cases of the 3243 mutation associated with the MELAS syndrome.
The finding of an abnormal mitochondrial genome in the endothelium and smooth muscle of cerebral vessels has been suggested as a basis for the strokes and migraine headaches.

Question 23

בת 23 עם התפתחות תקינה מלבד גובה נמוכה. בשנים אחרונות כאבי ראש המיקרניאלים פולסטיליים בחלקם מלווה בטשטוש ראיה. מזה שלושה ימים לאחר שחלתה בדלקת ריאות, הופיעו כאבי ראש המיקרניאלים ימנים קשים, מלווים בהקאות, בהמשך טשטוש ראיה, מצב בילבולים ופרכוסים.
בMRI
מוח הודגמו מוקדים היפראינטסיים בT2
באיזורים אחורים של המוח, כולל קורטקס וחומר הלבן תת קורטיקלי אשר לא מכבדים גבולות ווסקולארים. מה היא אבחנה סבירה:

1. Fabry
2. CADASIL
3. PRES
4. Moyamoya
5. MELAS

Answer 23

MELAS
* Mitochondrial Encephalomyopathy; Lactic Acidosis; Stroke like episodes.
* mtDNA point mutatuins
* mitochondrial proliferation
* multi system disease.
* axonal neuropathy (areflexia)
* biopsy= ragged red fibers
—–

MELASMitochondrial Encephalomyopathy, lactic acidosis and stroke like episodes

normal early development followed by poor growth, focal or generalized seizures, and recurrent acute episodes that resemble strokes or prolonged transient ischemic attacks.
The stroke deficits often improve but in some cases lead to a progressive encephalopathy.
Some have hemicranial headaches that cannot be distinguished from migraine, and others suffer repetitive vomiting or episodic lactic acidosis.
If there is a characteristic feature it is the unusual clinical pattern of focal seizures, sometimes prolonged, which herald a stroke and produce an unusual radiographic pattern of infarction involving the cortex and immediate subcortical white matter. The CT may also show numerous low-density regions that have no clinical correlates.
Most patients have ragged red fibers in muscle but only rarely is there weakness or exercise intolerance.
Approximately 80 percent of MELAS cases are related to a mitochondrial mutation occurring at the 3243 site of the mitochondrial gene or, in a few instances, at an alternative locus that also codes for a segment of transfer RNA.
Maternal inheritance is common but sporadic cases are well known.
only half of the cases of the 3243 mutation associated with the MELAS syndrome.
The finding of an abnormal mitochondrial genome in the endothelium and smooth muscle of cerebral vessels has been suggested as a basis for the strokes and migraine headaches.

Question 24

תיאור של מטופלת צעירה עם סכרת ומיגרנה, מתקבלת עם אירוע הפרעה בשדה ראיה ללא כאב ראש, בהדמיה נראה נגע אוקסיפיטלי שמאלי. לאחר 3 שבועות הופעה של חולשה בפלג גוף שמאל והפרעת הראיה חלפה. ב
FLAIR נגע פרונטלי ימני והנגע האוקסיפיטלי נעלם.
אמא של המטופלת סובלת מירידה קוגניטיבית מגיל צעיר. מה האבחנה הסבירה?
1. קאדאסיל
2. מחלת MELAS
3. פברי

Answer 24

MELAS

MELAS
* Mitochondrial Encephalomyopathy; Lactic Acidosis; Stroke like episodes.
* mtDNA point mutatuins
* mitochondrial proliferation
* multi system disease.
* axonal neuropathy (areflexia)
* biopsy= ragged red fibers
—–

MELASMitochondrial Encephalomyopathy, lactic acidosis and stroke like episodes

normal early development followed by poor growth, focal or generalized seizures, and recurrent acute episodes that resemble strokes or prolonged transient ischemic attacks.
The stroke deficits often improve but in some cases lead to a progressive encephalopathy.
Some have hemicranial headaches that cannot be distinguished from migraine, and others suffer repetitive vomiting or episodic lactic acidosis.
If there is a characteristic feature it is the unusual clinical pattern of focal seizures, sometimes prolonged, which herald a stroke and produce an unusual radiographic pattern of infarction involving the cortex and immediate subcortical white matter. The CT may also show numerous low-density regions that have no clinical correlates.
Most patients have ragged red fibers in muscle but only rarely is there weakness or exercise intolerance.
Approximately 80 percent of MELAS cases are related to a mitochondrial mutation occurring at the 3243 site of the mitochondrial gene or, in a few instances, at an alternative locus that also codes for a segment of transfer RNA.
Maternal inheritance is common but sporadic cases are well known.
only half of the cases of the 3243 mutation associated with the MELAS syndrome.
The finding of an abnormal mitochondrial genome in the endothelium and smooth muscle of cerebral vessels has been suggested as a basis for the strokes and migraine headaches.

Question 25

תיאור של חולה עם ווילסון למה אפשר לצפות לאחר התחלת הטיפול?  1. שיפור במשקע החום בעין  2. -העדר שיפור תפקודי כבד  3. ירידה בהפרשה של נחושת בשתן  4. מיאסניה סרונגטיבית 

Answer 25

שיפור במשקע החום בעין. ## Footnote מקרא לציורים: * י**רוק –כוראה** * צהוב –אטקסיה * **כחול :סימנים פירמידליים** * שוט – שמחזיקים-AD שנחבטים –AR * משקפיים –עיוורון * אוזניות-פגיעה בשמיעה * גפיים בכתום-פולינירופתיה * כובע-ורוד-שינוי התנהגות * **צירים –EPS** * ברקים כחולים –מיוקולוניות * **שן אחת –דמנציה** * שפם –גנטיקה XLINKED * אדום –מיופתיה? * דגנר\קטיבי – כחול טאופאטיה ,צהוב סינקלופתיה * פסים ורודים –דרמטולוגיה * אדום ורוד -פוליניורופתיה

Question 26

Answer 26

לא משתמשים בפוטסיום סולפאט כטיפול בווילסון. As the disease progresses, the “**classic syndrome**" evolves: **dysphagia and drooling, rigidity and slowness** of movements of the limbs; **flexed limb postures; fixity of facial muscles with *mouth constantly agape***, giving an appearance of grinning or a **"vacuous smile"; dysarthria or virtual anarthria** (bulbar extrapyramidal syndrome); and a **tremor in repose that increases when the limbs are outstretched to a coarse, *"wing-beating“* movement**. **Slowed saccadic** eye movements and **limitation of upgaze** are also characteristic. A **notable feature is the tendency for the motor disorders to be concentrated in the bulbar musculature and to spread caudally**. Thus, the syndrome differs from classic parkinsonism. Usually **elements of cerebellar ataxia and intention tremor of variable degree are added at some stage of the disease**. Approximately **6 percent of patients develop seizures** (Dening et al). Gradually the disability increases because of increasing rigidity and tremor. The patient **becomes mute, immobile, extremely rigid, dystonic, and *slowed mentally*, the latter usually being a *late and variable* effect.** With progression of the neurologic disease, the **Kayser-Fleischer rings** become more evident. * **Treatment** before the appearance of neurologic signs;, neurologic deterioration can be prevented to a large extent. Treatment consists of (1) **reduction of dietary copper** avoidance of copper-rich foods (liver, mushrooms, cocoa, chocolate, nuts, and shellfish (2) **copper chelating agent *d-penicillamine*** (1 to 3 g/d) by mouth, in divided doses. **Pyridoxine** 25 mg/d should be added in order to **prevent anemia**. The use of d-penicillamine is associated with a number of problems. *Sensitivity reactions to the drug (rash, arthralgia, fever, leukopenia)* develop in 20 percent of patients and require a temporary reduction of dosage or a *course of prednisone* to bring them under control. Reinstitution of drug therapy should then be undertaken, using low dosages (250 mg daily) and, later, small, widely spaced increases. If the patient is still sensitive to d-penicillamine or if *severe reactions (lupus-like or nephrotic syndromes or myasthenia gravis)* occur, the drug should be discontinued and **another chelating agent, *triethylene tetramine* (trientine) or *ammonium tetrathiomolybdate*** may be substituted. **Zinc**, which blocks the intestinal absorption of copper, is also a suitable treatment, but ineffective alone. It is given as zinc acetate, 100 to 150 mg daily in 3 to 4 divided doses at least 1 h before meals (Hoogenraad et al). The appropriate drug must then be continued for the patient’s ## Footnote מקרא לציורים: * י**רוק –כוראה** * צהוב –אטקסיה * **כחול :סימנים פירמידליים** * שוט – שמחזיקים-AD שנחבטים –AR * משקפיים –עיוורון * אוזניות-פגיעה בשמיעה * גפיים בכתום-פולינירופתיה * כובע-ורוד-שינוי התנהגות * **צירים –EPS** * ברקים כחולים –מיוקולוניות * **שן אחת –דמנציה** * שפם –גנטיקה XLINKED * אדום –מיופתיה? * דגנר\קטיבי – כחול טאופאטיה ,צהוב סינקלופתיה * פסים ורודים –דרמטולוגיה * אדום ורוד -פוליניורופתיה

Question 27

מה המשותף להפרעה בתנועות עיניים של ווילסון, הנטינגטון ואטקסיה טלנגיאקטזיה 1. העדר סקאדות 2. סקאדות היפומטריות 3. סקאדות איטיות 4. סקאדות היפרמטריות 5. קושי בהחזקת מבט לטראלי של העין שעושה אדוקציה

Answer 27

סקאדות איטיות נראה גם בווילסון, הנטינגטון ואטקסיה טלנגיאקטזיה * **Wilsons**: **Slowed saccadic eye movements and *limitation of upgaze*** are also characteristic. A notable feature is the tendency for the motor disorders to be concentrated in the bulbar musculature and to spread caudally. * **Ataxia- Telangiectasa**: The **eye movements become jerky; with slow and long-latency saccades**, and there is also **apraxia for voluntary gaze** (the patient turns the head but not the eyes on attempting to look to the side). This movement of the head and eyes in tandem is the most specific feature of the process. **Optokinetic nystagmus is lost** and reading becomes all but impossible. * **Huntington’s disease**: Particularly characteristic are **impaired initiation and slowness of both pursuit and volitional saccadic movements** and an ***inability to make a volitional saccade without movement of the head.*** Excessive distractibility may be noticed during attempted ocular fixation. The patient feels compelled to glance at extraneous stimuli even when specifically instructed to ignore them. **Upward gaze** is often impaired as the illness progresses. --------- Side comment: Pursuit is impaired toward the side of a parietal lesion and away from a frontal lesion,

Question 28

Answer 28

FABRY- alpha galactosidase * X linked – recessive * In males * Deficeincy of alpha-galactosidase * Accumulation of ceramide in endothelial, perithelial, SM of blood vessels and renal tubular and glomerular cells * Childhood – adolescence – intemrittent lancinating pain and dysethesia * Increased by fever, hot weather, exercise. * Htn, renal involvement, cardiomegaly, MI, thrombotic infarctions * Angiokeratomas * * Enzyme replacement therapy ----- The disease becomes manifest clinically in **childhood or adolescence**, with **intermittent lancinating pains** and dysesthesias of the extremities. A notable feature of these pains is their **evocation by fever, hot weather, and vigorous exercise**. Usually there is no sensory loss, but autonomic disturbances have been recorded in a series of our cases. **Many years later** there is a diffuse **vascular involvement that leads to hypertension, *renal* damage, cardiomegaly, and myocardial ischemia**. **Thrombotic infarctions occur in the brain** during early adult years. Occasional cases are discovered in adulthood with confluent cerebral white matter changes on MRI and progressive problems such as dysarthria. The **characteristic angiokeratomas** tend to be most prominent **periumbilically** and resemble small angiomas that obliterate slightly with pressure. Desnick and colleagues have reviewed the neurologic, neuropathologic, and biochemical findings in this disease, and Cable and colleagues have written informatively on the autonomic aspects. **Treatment Enzyme replacement** ---------- 1 – Alpha Glucosidase – Pompe (Acid Maltase) - ?no mention of B glucosidase in Adams glucocerebrosidase 2 – Gaucher hexosaminidase A 3– Tay Sachs 4 – Fabry Alfa galactosidase ## Footnote מקרא לציורים: * ירוק –כוראה * צהוב –אטקסיה * כחול :סימנים פירמידליים * שוט – שמחזיקים-AD שנחבטים –AR * משקפיים –עיוורון * אוזניות-פגיעה בשמיעה * גפיים בכתום-פולינירופתיה * כובע-ורוד-שינוי התנהגות * צירים –EPS * ברקים כחולים –מיוקולוניות * שן אחת –דמנציה * **שפם –גנטיקה XLINKED** * אדום –מיופתיה? * דגנר\קטיבי – כחול טאופאטיה ,צהוב סינקלופתיה * פסים ורודים –דרמטולוגיה * **אדום ורוד -פוליניורופתיה**

Question 29

תיאור של ילד עם מיוקלוניות , אפילפסיה , אטקסיה. נאמר בשאלה שמדובר ב Lafora body epilepsy . מה תמצא ?  א. גם לאמא ולסבתא יש אותה מחלה  ב. מצבורי גליקוגן  ג. occipital seizure    

Answer 29

OCCIPITAL SEIZURES ## Footnote מקרא לציורים: * ירוק –כוראה * **צהוב –אטקסיה** * כחול :סימנים פירמידליים * שוט – שמחזיקים-AD שנחבטים –AR * משקפיים –עיוורון * אוזניות-פגיעה בשמיעה * גפיים בכתום-פולינירופתיה * **כובע-ורוד-שינוי התנהגות** * **צירים –EPS** * **ברקים כחולים –מיוקולוניות** * **שן אחת –דמנציה** * שפם –גנטיקה XLINKED * אדום –מיופתיה? * דגנר\קטיבי – כחול טאופאטיה ,צהוב סינקלופתיה * פסים ורודים –דרמטולוגיה * אדום ורוד -פוליניורופתיה

Question 30

בת 16 , עם התפתחות תקינה עד כה. מזה חצי שנה סובלת ממיוקלונוס, הזיות ראיה ופרכוסים טוניים- קלוניים, הפרעת התנהגות וקשיים לימודיים. בדיקות דם, נוזל שדרה, פונדוס ו- MRI מוח תקינים. מה צפוי ביותר למצוא בבדיקה פתולוגית? א. “fingerprint” pattern inclusions in skin biopsy ב. PAS positive bodies composed of polyglucosan in skin biopsy ג. red ragged fibers in muscle biopsy ד. sialidase deficiency in cultured fibroblasts

Answer 30

PAS positive bodies composed of polyglucosan in skin biopsy (lafora bodies) -------------- המסיחים: א. **Juvenile Ceroid Lipofuscinosis** (Batten Disease, CLN3 Mutation) **severe myoclonus, seizures, and visual loss**. In the juvenile type, the **first lesions are seen in the maculae; yellow-gray areas of degeneration** Stages: **visual** impairment, followed by **generalized seizures and myoclonus**, often with **irritability, poor control of emotions, and stuttering, jerky speech** at 2 years, then gradual **intellectual deterioration** to which were added **cerebellar ataxia and intention tremor**, Finally, the patient lies **curled up in bed, blind and speechless, with strong extensor plantar reflexes, occasionally adopting dystonic postures**. Batten disease is caused by **CLN3, which codes battenin**, a lysosomal transmembrane protein but its function is currently not known. In the early stages, the **EEG pattern of random, high-voltage, triphasic waves is diagnostic**; **later**, as the seizures and myoclonic jerks become less frequent and finally cease, **only delta waves remain**. **“fingerprint” pattern in electron microscopic study of biopsy material, particularly of the eccrine sweat glands of the skin** ג. MERRF- myoclonic epilepsy/ataxia ד. cherry red spot myoclonus syndrome/ type 1 sialidosis ## Footnote מקרא לציורים: * ירוק –כוראה * צהוב –אטקסיה * כחול :סימנים פירמידליים * שוט – שמחזיקים-AD שנחבטים –AR * משקפיים –עיוורון * אוזניות-פגיעה בשמיעה * גפיים בכתום-פולינירופתיה * כובע-ורוד-שינוי התנהגות * צירים –EPS * ברקים כחולים –מיוקולוניות * שן אחת –דמנציה * שפם –גנטיקה XLINKED * אדום –מיופתיה? * דגנר\קטיבי – כחול טאופאטיה ,צהוב סינקלופתיה * פסים ורודים –דרמטולוגיה * אדום ורוד -פוליניורופתיה

Question 31

מאפיינים כלליים של המחלות המטובליות המולדות

Answer 31

* Adrenoleukodystrophy – VLCFA / ABCD1 X Linker Recessive * Metachormatic – Arylsulfatase * Krabbe – Galactocerbrosidase * Fabry- Alpha Galactosidase * Tay Sachs – GM2 Gangiloside, Hexosaminidase A * Sandhoff – Hexosaminidase A and B * Gaucher – Glucocerebrosidase * Lafora Body – has Polyglucosan inclusion bodies (different from adult polyglucosan disease)

Question 32

Figure 36-1. Retinal cherry red spot in a patient with Tay Sachs disease. The whitish ring surrounds the dark macula. In this dark skinned child, the macular spot is dark rather than reddish. (Courtesy of Dr. Shirley Wray.)

Answer 32

Question 33

Figure 36-2. Krabbe disease. Axial T2weighted MRI of a 6month old with difficulty feeding, irritability, upper extremity hypertonia and lower extremity hypotonia, which began at 3 months. Laboratory testing confirmed low levels of leukocyte galactocerebrosidase activity. There is abnormal hyperintensity of the cerebral peduncles (corticospinal tract atrophy) as well as enlargement of the prechiasmatic optic nerves. Thalamic hypointensity, not shown here, is a common finding as well. (Image courtesy of Drs. Edward Yang and Sanjay Prabhu.)

Answer 33

Question 34

Figure 36-3. Spongy degeneration of infancy (Canavanvan Bogaert Bertrand disease). Axial T2weighted MRI of a 5week old with hypertonia, nystagmus, and macrocephaly. There is abnormal hyperintensity in the globus pallidus, ventrolateral thalamus, and internal capsule. Abnormal white matter hyperintensity extends to the cortex without sparing of the arcuate fibers. MR spectroscopy (not shown) revealed a markedly elevated Nacetyl aspartate peak. (Image courtesy of Drs. Edward Yang and Sanjay Prabhu.)

Answer 34

Figure 36-3. Spongy degeneration of infancy (Canavanvan Bogaert Bertrand disease). Axial T2weighted MRI of a 5week old with hypertonia, nystagmus, and macrocephaly. There is abnormal hyperintensity in the globus pallidus, ventrolateral thalamus, and internal capsule. Abnormal white matter hyperintensity extends to the cortex without sparing of the arcuate fibers. MR spectroscopy (not shown) revealed a markedly elevated Nacetyl aspartate peak. (Image courtesy of Drs. Edward Yang and Sanjay Prabhu.)

Question 35

Figure 36-4. A schematic for diagnosis of the inherited metabolic diseases of infancy. (Courtesy of Dr. Edwin Kolodny.)

Answer 35

Question 36

Neurologic signs that are more or less specific for certain metabolic diseases: 1. Acousticomotor obligatory startle: 2. Abolished tendon reflexes with definite Babinski signs: 3. Peculiar eye movements, pendular nystagmus, and head rolling: 4. Marked rigidity, opisthotonos, and tonic spasms: 5. Intractable seizures and generalized or multifocal myoclonus: 6. Intermittent hyperventilation: 7. Strabismus, hypotonia, seizures, lipodystrophy:

Answer 36

Neurologic signs that are more or less specific for certain metabolic diseases are as follows: 1. Acoustico-motor obligatory startle: Tay Sachs disease 2. Abolished tendon reflexes with definite Babinski signs: globoid cell (Krabbe) leukodystrophy, occasionally Leigh disease, and (beyond infancy) metachromatic leukodystrophy 3. Peculiar eye movements, pendular nystagmus, and head rolling: Pelizaeus-Merzbacher disease, Leigh disease; later, hyperbilirubinemia and Lesch- Nyhan hyperuricemia 4. Marked rigidity, opisthotonos, and tonic spasms: Krabbe, Alpers disease, or infantile Gaucher disease (classic triad: trismus, strabismus, opisthotonos) 5. Intractable seizures and generalized or multifocal myoclonus: Alpers disease 6. Intermittent hyperventilation: Leigh disease and congenital lactic acidosis (also nonprogressive familial agenesis of vermis) 7. Strabismus, hypotonia, seizures, lipodystrophy: carbohydrate deficient glycoprotein syndrome

Question 37

Ocular abnormalities of specific diagnostic value in this age group are as follows: 1. Rapid pendular nystagmus: 2. Macular cherry red spots: 3. Corneal opacification: 4. Cataracts:

Answer 37

Ocular abnormalities of specific diagnostic value in this age group are as follows: 1. Rapid pendular nystagmus: PelizaeusMerzbacher disease, rarely Krabbe leukodystrophy, Cockayne syndrome (later age) 2. Macular cherry-red spots: Tay Sachs disease and Sandhoff variant, some cases of infantile Niemann Pick disease, and rarely lipofuscinosis (see Table 364) 3. Corneal opacification: Lowe disease, infantile GM1 gangliosides; later, the mucopolysaccharidoses 4. Cataracts: galactosemia, Lowe disease, Zellweger disease (also congenital rubella)

Question 38

Several other medical findings are of specific diagnostic value: 1. Dysmorphic facies: 2. Enlarged liver and spleen: 3. Enlarging head without hydrocephalus (macrocephaly): 4. Beaking of vertebral bodies in radiographs: 5. Multiple arthropathies and raucous dysphonia: 6. Storage granules and vacuolated lymphocytes: 7. Abnormal histiocytes in marrow smears: 8. Colorless, friable hair:

Answer 38

Several other medical findings are of specific diagnostic value: 1. Dysmorphic facies: generalized GM1 gangliosidosis, Lowe and Zellweger syndromes, and some early cases of mucopolysaccharidosis and mucolipidosis 2. Enlarged liver and spleen: infantile Gaucher disease and Niemann Pick disease; one type of hyperammonemia; Sandhoff disease; later, the mucopolysaccharidoses and mucolipidoses 3. Enlarging head without hydrocephalus (macrocephaly): Canavan spongy degeneration of infancy, some cases of Tay Sachs disease, Alexander disease 4. Beaking of vertebral bodies in radiographs: GM1 gangliosidosis (and, at a more advanced age, the mucopolysaccharidoses, fucosidosis, mannosidosis, and the mucolipidoses) 5. Multiple arthropathies and raucous dysphonia: Farber disease 6. Storage granules and vacuolated lymphocytes: Niemann Pick disease, generalized GM1 gangliosidosis 7. Abnormal histiocytes in marrow smears: Gaucher cells, foamy histiocytes in Niemann Pick disease, generalized GM1 gangliosidosis and closely related diseases, Farber disease 8. Colorless, friable hair: Menkes disease

Question 39

The following are inherited metabolic diseases that become evident clinically in late infancy and early childhood:

Answer 39

The following are inherited metabolic diseases that become evident clinically in late infancy and early childhood: 1. Many of the milder disorders of amino acid metabolism 2. Metachromatic and other leukodystrophies 3. Late infantile GM1 gangliosidosis 4. Late infantile Gaucher disease and NiemannPick disease 5. Neuroaxonal dystrophy 6. The mucopolysaccharidoses 7. The mucolipidoses 8. Fucosidosis 9. The mannosidoses 10. Aspartylglycosaminuria 11. Ceroid lipofuscinosis (JanskyBielschowsky disease) 12. Cockayne syndrome

Question 40

The persistent cerebellar ataxias of childhood in which a metabolic fault or mutation has been demonstrated are as follows:

Answer 40

1. Refsum disease 2. Abetalipoproteinemia (BassenKornzweig syndrome) 3. Ataxiatelangiectasia (see Chap. 37) 4. Galactosemia 5. Friedreich ataxia

Question 41

Figure 36-5. Metachromatic leukodystrophy. Axial T2 weighted MRI of a 2 year old girl with developmental regression and EMG evidence of diffuse motor and sensory demyelination. There is abnormal symmetric central white matter hyperintensity with sparing of the subcortical arcuate fibers. (Image courtesy of Drs. Edward Yang and Sanjay Prabhu.)

Answer 41

Question 42

Which Metabolic Diseases of Late Infancy and Early Childhood express: 1. Evidence of involvement of peripheral nerves (weakness, hypotonia, areflexia, sensory loss, reduced conduction velocities) in conjunction with lesions of the CNS:

Answer 42

1. Evidence of involvement of peripheral nerves (weakness, hypotonia, areflexia, sensory loss, reduced conduction velocities) in conjunction with lesions of the CNS—metachromatic leukodystrophy, Krabbe leukodystrophy, neuroaxonal dystrophy, and Leigh disease

Question 43

Which Metabolic Diseases of Late Infancy and Early Childhood express the following ophthalmic signs: a. Corneal clouding—

Answer 43

a. Corneal clouding—several of the mucopolysaccharidoses (Hurler, Scheie, Morquio, Maroteaux-Lamy), mucolipidoses, tyrosinemia, aspartylglycosaminuria (rare)

Question 44

Which Metabolic Diseases of Late Infancy and Early Childhood express the following ophthalmic signs: b. Cherry-red macular spot—

Answer 44

b. Cherry- red macular spot—GM2 gangliosidosis, GM1 gangliosidosis (half the cases), lipomucopolysaccharidosis, occasionally NiemannPick disease

Question 45

Which Metabolic Diseases of Late Infancy and Early Childhood express the following ophthalmic signs: c. Retinal degeneration with pigmentary deposits—

Answer 45

c. Retinal degeneration with pigmentary deposits—Jansky Bielschowsky lipid storage disease, GM1 gangliosidosis, syndrome of sea-blue histiocytes

Question 46

Which Metabolic Diseases of Late Infancy and Early Childhood express the following ophthalmic signs: d. Optic atrophy and blindness—

Answer 46

d. Optic atrophy and blindness—metachromatic leukodystrophy, neuroaxonal dystrophy

Question 47

Which Metabolic Diseases of Late Infancy and Early Childhood express the following ophthalmic signs: e. Cataracts—

Answer 47

e. Cataracts—Marinesco-Sjögren syndrome, Fabry disease, mannosidosis

Question 48

Which Metabolic Diseases of Late Infancy and Early Childhood express the following ophthalmic signs: f. Ocular apraxia—

Answer 48

f. Ocular apraxia—ataxia telangiectasia, Niemann Pick disease

Question 49

Which Metabolic Diseases of Late Infancy and Early Childhood express the following ophthalmic signs: g. Impairment of vertical eye movements—

Answer 49

g. Impairment of vertical eye movements—late infantile Niemann Pick disease, juvenile dystonic lipidosis, sea blue histiocyte syndrome, Wilson disease.

Question 50

Which Metabolic Diseases of Late Infancy and Early Childhood express the following ophthalmic signs: h. Jerky eye movements, limited abduction—

Answer 50

h. Jerky eye movements, limited abduction—late infantile Gaucher disease

Question 51

Which Metabolic Diseases of Late Infancy and Early Childhood express Extrapyramidal signs—

Answer 51

3. Extrapyramidal signs—late onset Niemann Pick disease (rigidity, abnormal postures), juvenile dystonic lipidosis (dystonia, choreoathetosis), Rett, ataxia telangiectasia (athetosis), Sanfilippo mucopolysaccharidosis, type I glutaric acidemia, Wilson disease, Segawa dopa responsive dystonia

Question 52

Which Metabolic Diseases of Late Infancy and Early Childhood express 4. Facial dysmorphism—

Answer 52

4. Facial dysmorphism—Hurler, Scheie, Morquio, and Maroteaux-Lamy forms of mucopolysaccharidosis, aspartylglycosaminuria, mucolipidoses, GM1 gangliosidosis, mannosidosis, fucosidosis (some cases), multisulfatase deficiencies (Austin), some mitochondrial disorders

Question 53

Which Metabolic Diseases of Late Infancy and Early Childhood express 5. Dwarfism, spine deformities, arthropathies—

Answer 53

5. Dwarfism, spine deformities, arthropathies—Hurler, Morquio, and other mucopolysaccharidoses, Cockayne syndrome

Question 54

Which Metabolic Diseases of Late Infancy and Early Childhood express 6. Enlarged liver and spleen—

Answer 54

6. Enlarged liver and spleen—NiemannPick disease, Gaucher disease, all mucopolysaccharidoses, fucosidosis, mucolipidoses, GM1 gangliosidosis

Question 55

Which Metabolic Diseases of Late Infancy and Early Childhood express 7. Alterations of skin—

Answer 55

7. Alterations of skin—photosensitivity (Cockayne syndrome and one form of porphyria); papular nevi and angiokeratoma (Fabry disease, fucosidosis); telangiectasia of ears, conjunctiva, chest (ataxiatelangiectasia); ichthyosis (Sjögren Larsen disease, caused by fatty alcohol dehydrogenase deficiency); plaquelike lesions in Hunter syndrome

Question 56

Which Metabolic Diseases of Late Infancy and Early Childhood express 8. Beaked thoracolumbar vertebrae—

Answer 56

8. Beaked thoracolumbar vertebrae—all mucopolysaccharidoses, mucolipidoses, mannosidosis, fucosidosis; aspartylglycosaminuria, multiple sulfatase deficiencies

Question 57

Which Metabolic Diseases of Late Infancy and Early Childhood express 9. Deafness—

Answer 57

9. Deafness—mucopolysaccharidoses, mannosidosis, Cockayne syndrome

Question 58

Which Metabolic Diseases of Late Infancy and Early Childhood express 10. Hypertrophied gums—

Answer 58

10. Hypertrophied gums—mucolipidoses, mannosidosis

Question 59

Which Metabolic Diseases of Late Infancy and Early Childhood express 11. Vacuolated lymphocytes—

Answer 59

11. Vacuolated lymphocytes—all mucopolysaccharidoses, mucolipidoses, mannosidosis, fucosidosis

Question 60

Which Metabolic Diseases of Late Infancy and Early Childhood express 12. Granules in neutrophils—

Answer 60

12. Granules in neutrophils—all mucopolysaccharidoses, mucolipidoses, mannosidosis, fucosidosis, multiple sulfatase deficiencies

Question 61

Figure 36-6. Differential diagnosis of mucopolysaccharidoses from oligosaccharidoses. (Courtesy of Dr. Ed Kolodny.)

Answer 61

Figure 36-6. Differential diagnosis of mucopolysaccharidoses from oligosaccharidoses. (Courtesy of Dr. Ed Kolodny.)

Question 62

Figure 36-7. Kayser- Fleischer corneal ring in Wilson disease. Brown coloration is seen near the limbus of the cornea and represents copper deposition in Descemet’s membrane. (Reproduced from Mackay D, Miyawaki E: Hyperkinetic Movement Disorders. ACP Medicine, Online S12C17, Topic ID 1271. © Decker Intellectual Properties. Courtesy of Drs. Edison Miyawaki and Donald Bienfang.)

Answer 62

Question 63

Figure 36- 8. Pantothenate kinase associated neurodegeneration (Hallervorden- Spatz disease). T2- weighted MRI showing areas of decreased signal intensity of the pallidum bilaterally (corresponding to iron deposition) and a central high signal area because of necrosis (“eye of the tiger” sign). (Reproduced with permission from Lyon et al. Courtesy of Dr. C. Gillain.)

Answer 63

Question 64

Figure 36-9. Idiopathic basal ganglionic and cerebellar calcification discovered in a 54 year old woman with a slowly progressive rigid Parkinson syndrome.

Answer 64

Figure 36-9. Idiopathic basal ganglionic and cerebellar calcification discovered in a 54 year old woman with a slowly progressive rigid Parkinson syndrome.

Question 65

clinical subtypes of ALD:

Answer 65

1. A progressive degeneration of cerebral white matter in young males, often with cortical blindness—the classic type, accounting for half of all cases 2. An intermediate form in juvenile or young adult males with cerebral and spinal involvement (5 percent of cases) 3. A progressive spinal cord tract degeneration in adult males (25 percent of cases) 4. A chronic mild, nonprogressive spastic paraparesis in heterozygous female carriers (10 percent of cases) 5. Familial instances of Addison disease without neurologic involvement in males (10 percent of cases) 6. Possibly, in male infants, a form originating at birth (e.g., Zellweger disease)

Question 66

Figure 36-10. Adrenoleukodystrophy. Axial T2 weighted MRI of an 8 year old boy with headache. There is abnormal posterior periventricular white matter hyperintensity extending across the splenium of the corpus callosum. Laboratory testing confirmed adrenal insufficiency. (Image courtesy of Drs. Edward Yang and Sanjay Prabhu.)

Answer 66

Question 67

metabolic disorders that may demonstrate regression of cognitive function in association with personality change and alteration of behavior in an adult—

Answer 67

1. Wilson disease 2. Adrenoleukodystrophy 3. Metachromatic leukodystrophy 4. PKAN pigmentary degeneration 5. Late onset neuronal ceroid lipofuscinosis (Kufs form) 6. Juvenile and adult Gaucher disease (type III) 7. Some of the mucopolysaccharidoses 8. Adult GM2 gangliosidosis 9. Mucolipidosis I (type I sialidosis) 10. Lafora body myoclonic epilepsy 11. Non wilsonian copper disorder (hereditary ceruloplasmin deficiency)

Question 68

metabolic diseases, the onset of which was in adult life:

Answer 68

1. Metachromatic leukoencephalopathy 2. Adrenoleukodystrophy 3. Globoid body leukodystrophy (Krabbe disease) 4. Kufs form of neuronal ceroid lipofuscinosis 5. GM2 gangliosidosis 6. Wilson disease 7. Gaucher disease 8. Niemann Pick disease 9. Carnitine palmityl transferase deficiency 10. Mucopolysaccharide encephalopathy 11. Mucolipidosis type I 12. Polyneuropathies (Andrade disease, Fabry disease, porphyria, Refsum disease) 13. Mitochondrial diseases, particularly progressive external ophthalmoplegia and Leigh disease