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Encephalopathy, porphyria-related(ENCEP)

MedGen UID:
1859316
Concept ID:
C5935574
Disease or Syndrome
Synonym: ENCEP
 
Gene (location): HMBS (11q23.3)
 
Monarch Initiative: MONDO:0958224
OMIM®: 620704

Definition

Porphyria-related encephalopathy (ENCEP) is an autosomal recessive disorder characterized by the onset of progressive neurologic abnormalities in early infancy. Features include global developmental delay, poor walking or inability to walk, impaired intellectual development, hypotonia, ataxia, dysarthria, spasticity, ocular abnormalities, and peripheral neuropathy. The disease course is usually rapidly progressive and may lead to death in childhood. Laboratory studies show increased plasma and urinary levels of the putatively neurotoxic porphyrin precursors delta-aminolevulinic acid (ALA), porphobilinogen (PBG), and uroporphyrin resulting from deficient HMBS enzymatic activity (Solis et al., 2004). [from OMIM]

Clinical features

From HPO
Orange urine
MedGen UID:
605940
Concept ID:
C0427825
Finding
An abnormal orange color of urine.
Red urine
MedGen UID:
910906
Concept ID:
C0858862
Finding
An abnormal red color of the urine.
Increased urine urobilinogen
MedGen UID:
1630944
Concept ID:
C2938867
Finding
An elevated concentration of urobilinogen in the urine.
Elevated urinary coproporphyrin level
MedGen UID:
1863707
Concept ID:
C5937299
Finding
The amount of a coproporphyrin in the urine, normalized for urine concentration, is above the upper limit of normal.
Postnatal growth retardation
MedGen UID:
395343
Concept ID:
C1859778
Finding
Slow or limited growth after birth.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Febrile seizure (within the age range of 3 months to 6 years)
MedGen UID:
3232
Concept ID:
C0009952
Disease or Syndrome
A febrile seizure is any type of seizure (most often a generalized tonic-clonic seizure) occurring with fever (at least 38 degrees Celsius) but in the absence of central nervous system infection, severe metabolic disturbance or other alternative precipitant in children between the ages of 3 months and 6 years.
Babinski sign
MedGen UID:
19708
Concept ID:
C0034935
Finding
Upturning of the big toe (and sometimes fanning of the other toes) in response to stimulation of the sole of the foot. If the Babinski sign is present it can indicate damage to the corticospinal tract.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Hyporeflexia
MedGen UID:
195967
Concept ID:
C0700078
Finding
Reduction of neurologic reflexes such as the knee-jerk reaction.
Sensorimotor neuropathy
MedGen UID:
207266
Concept ID:
C1112256
Disease or Syndrome
Delayed CNS myelination
MedGen UID:
867393
Concept ID:
C4021758
Anatomical Abnormality
Delayed myelination in the central nervous system.
Partial absence of cerebellar vermis
MedGen UID:
871190
Concept ID:
C4025667
Congenital Abnormality
Congenital absence of a part of the vermis of cerebellum.
Intention tremor
MedGen UID:
1642960
Concept ID:
C4551520
Sign or Symptom
A type of kinetic tremor that occurs during target directed movement is called intention tremor. That is, an oscillatory cerebellar ataxia that tends to be absent when the limbs are inactive and during the first part of voluntary movement but worsening as the movement continues and greater precision is required (e.g., in touching a target such as the patient's nose or a physician's finger).
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Kyphosis
MedGen UID:
44042
Concept ID:
C0022821
Anatomical Abnormality
Exaggerated anterior convexity of the thoracic vertebral column.
Axial hypotonia
MedGen UID:
342959
Concept ID:
C1853743
Finding
Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Hyperbilirubinemia
MedGen UID:
86321
Concept ID:
C0311468
Finding
An increased amount of bilirubin in the blood.
Reduced erythrocyte porphobilinogen deaminase activity
MedGen UID:
1853225
Concept ID:
C5872948
Finding
Activity or concentration of in the level of porphobilinogen deaminase (EC 4.3.1.8) in erythrocytes below the lower limit of normal.
Protruding tongue
MedGen UID:
66831
Concept ID:
C0241442
Finding
Tongue extending beyond the alveolar ridges or teeth at rest.
Coarse facial features
MedGen UID:
335284
Concept ID:
C1845847
Finding
Absence of fine and sharp appearance of brows, nose, lips, mouth, and chin, usually because of rounded and heavy features or thickened skin with or without thickening of subcutaneous and bony tissues.
Yellow-brown discoloration of the teeth
MedGen UID:
350813
Concept ID:
C1863008
Finding
Long philtrum
MedGen UID:
351278
Concept ID:
C1865014
Finding
Distance between nasal base and midline upper lip vermilion border more than 2 SD above the mean. Alternatively, an apparently increased distance between nasal base and midline upper lip vermilion border.
Ptosis
MedGen UID:
2287
Concept ID:
C0005745
Disease or Syndrome
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).
Cataract
MedGen UID:
39462
Concept ID:
C0086543
Disease or Syndrome
A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule.
Optic nerve hypoplasia
MedGen UID:
137901
Concept ID:
C0338502
Disease or Syndrome
Underdevelopment of the optic nerve.

Recent clinical studies

Etiology

Kevelam SH, Neeleman RA, Waisfisz Q, Friesema EC, Langendonk JG, van der Knaap MS
Neurology 2016 Sep 20;87(12):1258-65. Epub 2016 Aug 24 doi: 10.1212/WNL.0000000000003129. PMID: 27558376

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