Table 1 Clinical features and outcome following treatment of the three patients with biallelic SLC5A6 mutations causing SMVT deficiency

From: Identification and targeted management of a neurodegenerative disorder caused by biallelic mutations in SLC5A6

Clinical features	This study—patient II-1	This study—patient II-2	Subramanian 2017
*Neurological*
Neurocognitive regression	Onset: 14 months	Onset: 12 months Post treatment: Neurocognitive progress^a -walking with assistance -4–6 word vocabulary -improved social interaction/attention -utilising cup and spoon	Onset: infantile Post treatment: Neurocognitive progress^b -walking with assistance -5-word vocabulary -improved social interaction/personality
Microcephaly	Yes, relative^c	Yes, relative^c	Yes
Neuro-ophthalmological	Left esotropia	Nystagmus Dyskinetic saccades Binocular esotropia Post treatment: Nystagmus marked reduction	Nystagmus Post treatment: Nystagmus resolved
Spasticity	No	No	Yes
Hyperreflexia	Yes	Yes^d	NR
Seizures	No	Yes (well controlled) Post treatment: No significant change Reduced anticonvulsant requirement	NR
Hyperacusis	Yes	Yes (resolved pre-treatment)	NR
Peripheral neuropathy	NR	Mixed demyelinating & axonal sensorimotor polyneuropathy Post treatment: Electrographically resolved^e	NR
Neuroimaging (MRI)^f	No cerebral atrophy Right cerebellar haemorrhagic foci T2/FLAIR signal hyperintensity (periventricular & parieto-occipital white matter)	Cerebral atrophy (progressive) Cerebellar atrophy (progressive) Brainstem (pontine) atrophy Thin corpus callosum T2/FLAIR signal hyperintensity (central segmental tract & peritrigonal regions) Mega cisterna magna 1H-MRS (SVS) [31 and 144 ms; basal ganglia/frontoparietal white matter]: reduced NAA and broad lactate doublets	Cerebral atrophy Brainstem (pontine) atrophy Thin corpus callosum
Electroencephalogram (EEG)^g	Not done	Background slowing (encephalopathy) Epileptiform activity: generalised and multifocal spike-wave (2–3 Hz) Post treatment: Improved background rhythms^h Epileptiform activity reduced	Normal
Histopathology	Central nervous system: axonal spheroids Peripheral nervous system: undefined thickening Skeletal muscle biopsy: denervation atrophy	Cutaneous biopsy: membranous cytoplasmic inclusionsⁱ	Skeletal muscle biopsy: normal
*Gastrointestinal*
Feeding difficulties/ failure to thrive	Yes, bulbar dysfunction	Yes, bulbar dysfunction	Yes
Nasogastric tube/ gastrostomy feeding^j	Yes	Yes	Yes
GI haemorrhage	Yes^k	Yes^l	Yes^m
Other	GORD	Cyclical vomiting GORD Post treatment: cyclical vomiting improved	NR
*Cardiopulmonary*
	Asthma Right heart failureⁿ	Asthma tracheobronchomalacia ECG: non-specific ST & T-wave changes^o	NR
*Other*
Hypogammaglobulinemia	NR	Yes, Isolated IgG deficiency Post treatment: NR	Yes, IgG/IgA deficiency Post treatment: Resolved
Osteopenia	No	No	Yes Post treatment: Resolved
Digital clubbing	NR	Yes^p	NR
*Treatment*
	Nil	Biotin (intramuscular) 10 mg weekly Dexpanthenol (intramuscular) 250 mg weekly α-lipoic acid (intravenous) 300 mg weekly	Biotin (oral) 10–30 mg/day Pantothenic acid (oral) 250–500 mg/day α-Lipoic acid (oral) 150–300 mg/day

GORD gastro-oesophageal reflux disease, NR not reported
^aReported at +5 years from commencement of therapy
^bReported at +2 years, 9 months from commencement of therapy
^cRelative postnatal microcephaly (OFC growth retardation)
^dInitial hyperreflexia; progressive obtundation of myotatic reflexes presumed secondary to peripheral neuropathy
^eConfirmed by serial nerve conduction studies pre/post treatment
^fMost recent pre-treatment study [age]: II-1 [1 year, 12 months]; Supplementary Fig. 2A, II-2 [7 years, 5 months]; Supplementary Fig. 2B and C, Subramanian [12 months]
^gMost recent pre-treatment study [age]: II-2 [5 years, 5 months], Subramanian [6 months]
^hPost-treatment EEG [+4 years, 8 months]
ⁱSupplementary Fig. 3B
^jInsertion: II-1 (nasogastric tube [2 years, 7 months]; nil gastrostomy), II-2 (gastrostomy [6 years, 3 months]), Subramanian (nasogastric tube [infancy]; gastrostomy [6 months])
^kPerforated duodenal ulcer/duodenal artery
^lSuspected Mallory–Weiss tear in context of cyclical vomiting
^mReported secondary to thrombocytopenia
ⁿFeatures of right heart failure at autopsy, presumed secondary to pre-mortem cardiopulmonary resuscitation
^oNo clinical cardiomegaly and normal screening echocardiogram [8 years, 9 months]; non-specific ST segment and T wave changes present on ECG
^pDigital clubbing of uncertain aetiology (note: normal high-resolution chest CT)

Back to article page

Table 1 Clinical features and outcome following treatment of the three patients with biallelic SLC5A6 mutations causing SMVT deficiency

Search

Quick links