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Mitochondrial complex V (ATP synthase) deficiency, nuclear type 4A(MC5DN4A)

MedGen UID:
1841116
Concept ID:
C5830480
Disease or Syndrome
Synonym: MC5DN4A
 
Gene (location): ATP5F1A (18q21.1)
 
Monarch Initiative: MONDO:0957254
OMIM®: 620358

Definition

Mitochondrial complex V deficiency nuclear type 4A (MC5DN4A) is an autosomal dominant metabolic disorder characterized by poor feeding and failure to thrive in early infancy. Laboratory studies show increased serum lactate, alanine, and ammonia, suggesting mitochondrial dysfunction. Some affected individuals show spontaneous resolution of these symptoms in early childhood and have subsequent normal growth and development, whereas others show developmental delay with impaired intellectual development and movement abnormalities, including dystonia, ataxia, or spasticity; these neurologic deficits are persistent (Lines et al., 2021, Zech et al., 2022). For a discussion of genetic heterogeneity of mitochondrial complex V deficiency, nuclear types, see MC5DN1 (604273). [from OMIM]

Clinical features

From HPO
Oroticaciduria
MedGen UID:
78642
Concept ID:
C0268128
Finding
An increased concentration of orotic acid in the urine.
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
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.
Chronic diarrhea
MedGen UID:
96036
Concept ID:
C0401151
Finding
The presence of chronic diarrhea, which is usually taken to mean diarrhea that has persisted for over 4 weeks.
Cerebral palsy
MedGen UID:
854
Concept ID:
C0007789
Disease or Syndrome
Cerebral palsy describes a group of permanent disorders of the development of movement and posture, causing activity limitation, that are attributed to nonprogressive disturbances that occurred in the developing fetal or infant brain. The motor disorders of cerebral palsy are often accompanied by disturbances of sensation, perception, cognition, communication, and behavior, by epilepsy, and by secondary musculoskeletal problems.
Dystonic disorder
MedGen UID:
3940
Concept ID:
C0013421
Sign or Symptom
An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
Paraparesis
MedGen UID:
113150
Concept ID:
C0221166
Sign or Symptom
Weakness or partial paralysis in the lower limbs.
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.
Spastic tetraparesis
MedGen UID:
658719
Concept ID:
C0575059
Disease or Syndrome
Spastic weakness affecting all four limbs.
Acute encephalopathy
MedGen UID:
224930
Concept ID:
C1306587
Disease or Syndrome
A life-threatening disorder characterized by delirium, seizures, and neuromuscular changes.
Generalized dystonia
MedGen UID:
341342
Concept ID:
C1848954
Finding
A type of dystonia that affects all or most of the body.
Spastic ataxia
MedGen UID:
376528
Concept ID:
C1849156
Disease or Syndrome
Absent speech
MedGen UID:
340737
Concept ID:
C1854882
Finding
Complete lack of development of speech and language abilities.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Lactic acidosis
MedGen UID:
1717
Concept ID:
C0001125
Disease or Syndrome
An abnormal buildup of lactic acid in the body, leading to acidification of the blood and other bodily fluids.
Hyperprolinemia
MedGen UID:
75690
Concept ID:
C0268528
Disease or Syndrome
An increased concentration of proline in the blood.
Hyperglycinemia
MedGen UID:
82817
Concept ID:
C0268559
Disease or Syndrome
An elevated concentration of glycine in the blood.
Hyper-beta-alaninemia
MedGen UID:
75702
Concept ID:
C0268630
Disease or Syndrome
An increased concentration of alanine in the blood.
Increased circulating lactate concentration
MedGen UID:
332209
Concept ID:
C1836440
Finding
Abnormally increased level of blood lactate (2-hydroxypropanoic acid). Lactate is produced from pyruvate by lactate dehydrogenase during normal metabolism. The terms lactate and lactic acid are often used interchangeably but lactate (the component measured in blood) is strictly a weak base whereas lactic acid is the corresponding acid. Lactic acidosis is often used clinically to describe elevated lactate but should be reserved for cases where there is a corresponding acidosis (pH below 7.35).
Low plasma citrulline
MedGen UID:
326522
Concept ID:
C1839532
Finding
A decreased concentration of citrulline in the blood.
Hypoargininemia
MedGen UID:
892673
Concept ID:
C4025095
Finding
A decreased concentration of arginine in the blood.
Hyperglutamatemia
MedGen UID:
1671048
Concept ID:
C4732903
Finding
Concentration of glutamate in the blood circulation above the upper limit of normal.
Hyperammonemia
MedGen UID:
1802066
Concept ID:
C5574662
Laboratory or Test Result
An increased concentration of ammonia in the blood.

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