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Krabbe disease due to saposin A deficiency(KRBSAPA)

MedGen UID:
392873
Concept ID:
C2673266
Disease or Syndrome
Synonyms: Krabbe disease, atypical, due to saposin A deficiency; Saposin A Deficiency
SNOMED CT: Atypical Krabbe disease due to saposin A deficiency (1296731001)
 
Gene (location): PSAP (10q22.1)
 
Monarch Initiative: MONDO:0012720
OMIM®: 611722

Definition

Disease caused by homozygous mutation in the prosaposin gene (PSAP) on chromosome 10q22. The disease is genetically distinct from Krabbe disease. Clinical features include onset in infancy with respiratory and neurologic involvement. [from SNOMEDCT_US]

Clinical features

From HPO
Feeding difficulties
MedGen UID:
65429
Concept ID:
C0232466
Finding
Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Global brain atrophy
MedGen UID:
66840
Concept ID:
C0241816
Pathologic Function
Unlocalized atrophy of the brain with decreased total brain matter volume and increased ventricular size.
Tonic seizure
MedGen UID:
82855
Concept ID:
C0270844
Disease or Syndrome
A tonic seizure is a type of motor seizure characterized by unilateral or bilateral limb stiffening or elevation, often with neck stiffening.
Hyporeflexia
MedGen UID:
195967
Concept ID:
C0700078
Finding
Reduction of neurologic reflexes such as the knee-jerk reaction.
Vegetative state
MedGen UID:
182977
Concept ID:
C0917808
Disease or Syndrome
The absence of wakefulness and consciousness, but in contrast to a coma, there is involuntary opening of the eyes and movements such as teeth grinding, yawning, or thrashing of the extremities.
Peripheral axonal neuropathy
MedGen UID:
266071
Concept ID:
C1263857
Disease or Syndrome
An abnormality characterized by disruption of the normal functioning of peripheral axons.
Increased CSF protein concentration
MedGen UID:
329971
Concept ID:
C1806780
Finding
Increased concentration of protein in the cerebrospinal fluid.
Progressive neurologic deterioration
MedGen UID:
381506
Concept ID:
C1854838
Finding
Cerebral dysmyelination
MedGen UID:
343222
Concept ID:
C1854885
Finding
Defective structure and function of myelin sheaths of the white matter of the brain.
Hyperintensity of cerebral white matter on MRI
MedGen UID:
811125
Concept ID:
C2938912
Pathologic Function
A brighter than expected signal on magnetic resonance imaging emanating from the cerebral white matter.
Ventriculomegaly
MedGen UID:
480553
Concept ID:
C3278923
Finding
An increase in size of the ventricular system of the brain.
Hypertonia
MedGen UID:
10132
Concept ID:
C0026826
Finding
A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move.
Respiratory insufficiency
MedGen UID:
11197
Concept ID:
C0035229
Pathologic Function
Impairment of gas exchange within the lungs secondary to a disease process, neoplasm, or trauma, possibly resulting in hypoxia, hypercarbia, or both, but not requiring intubation or mechanical ventilation. Patients are normally managed with pharmaceutical therapy, supplemental oxygen, or both.
Respiratory failure
MedGen UID:
257837
Concept ID:
C1145670
Disease or Syndrome
A severe form of respiratory insufficiency characterized by inadequate gas exchange such that the levels of oxygen or carbon dioxide cannot be maintained within normal limits.
Central apnea
MedGen UID:
854403
Concept ID:
C3887548
Disease or Syndrome
Apnea resulting from depression of the respiratory centers in the medulla oblongata. There is a lack of respiratory effort rather than obstruction of airflow.

Recent clinical studies

Diagnosis

Calderwood L, Wenger DA, Matern D, Dahmoush H, Watiker V, Lee C
Mol Genet Metab 2020 Feb;129(2):161-164. Epub 2019 Aug 5 doi: 10.1016/j.ymgme.2019.08.001. PMID: 31439510
Spiegel R, Bach G, Sury V, Mengistu G, Meidan B, Shalev S, Shneor Y, Mandel H, Zeigler M
Mol Genet Metab 2005 Feb;84(2):160-6. doi: 10.1016/j.ymgme.2004.10.004. PMID: 15773042

Prognosis

Suzuki K
J Child Neurol 2003 Sep;18(9):595-603. doi: 10.1177/08830738030180090201. PMID: 14572137

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    Curated

    • ACMG ACT, 2022
      American College of Medical Genetics and Genomics, Newborn Screening ACT Sheet, Decreased galactocerebrosidase, elevated psychosine, Krabbe Disease (infantile form), 2022
    • ACMG Algorithm, 2022
      American College of Medical Genetics and Genomics, Algorithm, Krabbe disease: galactocerebrosidase deficiency, 2022

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